Mooney S M, Miller M W
Department of Psychiatry, University of Iowa College of Medicine, Iowa City, IA 52242-1000, USA.
Brain Res. 2001 Aug 17;911(1):71-81. doi: 10.1016/s0006-8993(01)02718-4.
Prenatal exposure to ethanol causes neuronal death in somatosensory cortex, but apparently not in the ventrobasal nucleus of the thalamus. Effectors such as bcl-2, bax, and caspase 3 can determine whether a neuron survives or dies. We hypothesize that ethanol differentially affects the expression of these proteins in the cortex and thalamus during the periods of naturally occurring and ethanol-induced neuronal death. Pregnant rats were fed ad libitum with an ethanol-containing liquid diet (Et) or pair-fed an isocaloric non-alcoholic diet (Ct). Samples were collected from fetuses (gestational day (G) 16 and G19) and pups (postnatal day (P) 0 through P30) and examined for bcl-2, bax, or caspase 3 expression using a quantitative immunoblotting procedure. Prenatal exposure to ethanol reduced cortical bcl-2 expression, but not bax expression on P6. Hence, the bcl-2/bax ratio was lower in Et-treated rats than in controls. In contrast, thalamic expression of neither bcl-2 nor bax was significantly different in the two groups of rats. Thus, the thalamic bcl-2/bax ratio was unaffected by exposure to ethanol. During the period of naturally occurring neuronal death, the expression of the active (20 kDa) and inactive isoforms (32 kDa) of caspase 3 was altered in the cortices of Et-treated rats, but not in their thalami. Thus, prenatal exposure to ethanol affected the early postnatal expression of death-related proteins in the cortex, but not in the thalamus. These biochemical changes concur with anatomical data on the spatial and temporal selectivity of ethanol toxicity in the developing CNS.
产前暴露于乙醇会导致体感皮层中的神经元死亡，但丘脑腹侧基底核中显然不会。诸如bcl-2、bax和半胱天冬酶3等效应分子可以决定神经元是存活还是死亡。我们假设，在自然发生的和乙醇诱导的神经元死亡期间，乙醇对皮层和丘脑中这些蛋白质的表达有不同的影响。给怀孕大鼠随意喂食含乙醇的液体饮食（Et组），或给其配对喂食等热量的无酒精饮食（Ct组）。从胎儿（妊娠第16天和第19天）和幼崽（出生后第0天至第30天）采集样本，并使用定量免疫印迹法检测bcl-2、bax或半胱天冬酶3的表达。产前暴露于乙醇会降低皮层中bcl-2的表达，但在出生后第6天不会降低bax的表达。因此，乙醇处理组大鼠的bcl-2/bax比值低于对照组。相比之下，两组大鼠丘脑bcl-2和bax的表达均无显著差异。因此，丘脑的bcl-2/bax比值不受乙醇暴露的影响。在自然发生的神经元死亡期间，半胱天冬酶3的活性（20 kDa）和无活性异构体（32 kDa）的表达在乙醇处理组大鼠的皮层中发生了改变，但在其丘脑中未发生改变。因此，产前暴露于乙醇会影响出生后早期皮层中与死亡相关蛋白质的表达，但不会影响丘脑中的表达。这些生化变化与发育中的中枢神经系统中乙醇毒性的空间和时间选择性的解剖学数据一致。
